T-Lymphocytes regulate the growth and differentiation of certain lymphopoietic andhaemopoietic cells through the release of various secreted protein factors [].These factors, which include interleukin-2 (IL2), are secreted by lectin- or antigen-stimulatedT-cells, and have various physiological effects. IL2 is a lymphokine that induces theproliferation of responsive T-cells. In addition, it acts on some B-cells, via receptor-specificbinding [], as a growth factor and antibody production stimulant []. Theprotein is secreted as a single glycosylated polypeptide, and cleavage of a signal sequenceis required for its activity []. Solution NMR suggests that the structure of IL2 comprises abundle of 4 helices (termed A-D), flanked by 2 shorter helices and several poorly-definedloops. Residues in helix A, and in the loop region between helices A and B, are important forreceptor binding. Secondary structure analysis has suggested similarity to IL4 and granulocyte-macrophage colony stimulating factor (GMCSF) [].
This entry represents interleukin-7 (IL7), it is a hematopoietic growth factor produced by bone marrow stromal cells. It promotes growth of B- and T-cell precursors and functions with IL2 in the activation of mature T-cells [, ]. IL-7 and IL-7Ralpha bind the gamma-c receptor forming a complex required for the development and homeostasis of T and B cells []. Interleukin-7 and Interleukin-9 belong to the same larger family.
This entry represents interleukin-7 (IL7), it is a hematopoietic growth factor produced by bone marrow stromal cells. It promotes growth of B- and T-cell precursors and functions with IL2 in the activation of mature T-cells [, ]. IL-7 and IL-7Ralpha bind the gamma-c receptor forming a complex required for the development and homeostasis of T and B cells []. Interleukin-7 and Interleukin-9 belong to the same larger family.
DOCK family members are evolutionarily conserved guanine nucleotide exchange factors (GEFs) for Rho-family GTPases []. DOCK proteins are required during several cellular processes, such as cell motility and phagocytosis. The N-terminal SH3 domain of the DOCK proteins functions as an inhibitor of GEF, which can be relieved upon its binding to the ELMO1-3 adaptor proteins, after their binding to active RhoG at the plasma membrane [, ]. DOCK family proteins are categorised into four subfamilies based on their sequence homology: DOCK-A subfamily (DOCK1/180, 2, 5), DOCK-B subfamily (DOCK3, 4), DOCK-C subfamily (DOCK6, 7, 8), DOCK-D subfamily (DOCK9, 10, 11) []. This entry represents DOCK2 (dedicator of cytokinesis 2). DOCK2 is involved in cytoskeletal rearrangements required for lymphocyte migration in response of chemokines. It activates RAC1 and RAC2, but not CDC42, by functioning as a guanine nucleotide exchange factor (GEF), which exchanges bound GDP for free GTP. It may also participate in IL2 transcriptional activation via the activation of RAC2 [].
This entry represents the SH3 domain of STAM1 (signal transducing adapter molecule 1). STAM1 is part of the endosomal sorting complex required for transport (ESCRT-0) and is involved in sorting ubiquitinated cargo proteins from the endosome []. It may also be involved in the regulation of IL2 and GM-CSF mediated signaling, and has been implicated in neural cell survival [, ]. STAMs were discovered as proteins that are highly phosphorylated following cytokine and growth factor stimulation []. They function in cytokine signaling and surface receptor degradation, as well as regulate Golgi morphology. They associate with many proteins including Jak2 and Jak3 tyrosine kinases [], Hrs, AMSH, and UBPY. STAM adaptor proteins contain VHS (Vps27, Hrs, STAM homology), ubiquitin interacting (UIM), and SH3 domains [].
